The immune system recognises pathogens and potential danger with pattern recognition receptors (PRR). This sensing induces innate and adaptive immune responses and often is the prerequisite of a timely and effective immune defence against pathogens. However, an excessive immune response is dangerous and potential fatal as in the case of sepsis.
Among different families of PRR the Toll-like receptors (TLRs) have been recognized as very important for the activation of several innate and adaptive immune responses. Within the last years many different endogenous as well as artificial agonists and ligands for TLRs have been identified including agonists for TLR1, TLR2, TLR3, TLR4, TLR5, TLR6, TLR7, TLR8, TLR9, and TLR11. For example, certain viral RNA as the agonists for TLR7 and TLR8 have been identified17. This knowledge allowed the use of TLR-ligands as adjuvants for the induction of superior immune responses in vaccines or in different therapies against infectious diseases and cancer. On the other hand this knowledge made it possible to interfere with unwanted immune responses by blocking TLR recognition. Examples of unwanted or exaggerated immune responses are autoimmune diseases, infection and sepsis. The immune responses induced by different TLR-agonists differ greatly, thus the identification of new TLR-agonists allows a more fine tuned application, e.g. as adjuvants.
Whereas TLR2, TLR4 and TLR9 are major host sensors of Gram-negative bacteria, TLR2 and TLR7 are believed to be central detectors of Gram-positive bacteria.1 Recognition of Gram-positive bacteria by TLR2 or TLR7 occurs via their lipoproteins, RNA and DNA, respectively2-5. However, the role of additional TLRs or other classes of PRRs such as C-type lectins, RIG-I-like helicases, or nucleotide binding domain- and leucine-rich repeat—containing proteins for detection of gram-positive bacteria is unclear. In particular, among the 13 different TLRs described in man and mouse the ligands for TLR10, TLR12 and TLR13 are unknown so far.
Thus, there is still a need for elucidating the role of TLRs in host protection from bacterial infection. In particular, it is an object to provide tools for targeting such TLRs, and methods and medical applications using them.